Survival of Naive CD4 T Cells: Roles of Restricting Versus Selecting MHC Class II and Cytokine Milieu

The diversity of naive CD4 T cells plays an important role in the adaptive immune response by ensuring the capability of responding to novel pathogens. In the past, it has been generally accepted that naive CD4 T cells are intrinsically long-lived; however, there have been studies suggesting some CD...

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Bibliographic Details
Published in:The Journal of immunology (1950) 1999-04, Vol.162 (7), p.3795-3801
Main Authors: Boursalian, Tamar E, Bottomly, Kim
Format: Article
Language:English
Subjects:
Adjuvants, Immunologic - physiology
AIDS/HIV
Animals
CD4 Lymphocyte Count
CD4-Positive T-Lymphocytes - cytology
CD4-Positive T-Lymphocytes - immunology
CD4-Positive T-Lymphocytes - metabolism
Cell Survival - immunology
Clonal Deletion
Cytokines - physiology
Histocompatibility Antigens Class II - immunology
Histocompatibility Antigens Class II - physiology
Interleukin-4 - physiology
Interleukin-7 - physiology
Mice
Mice, Inbred A
Mice, Inbred C57BL
Mice, Transgenic
Peptides - immunology
Peptides - metabolism
Thymectomy
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Summary:The diversity of naive CD4 T cells plays an important role in the adaptive immune response by ensuring the capability of responding to novel pathogens. In the past, it has been generally accepted that naive CD4 T cells are intrinsically long-lived; however, there have been studies suggesting some CD4 T cells are short-lived. In this report, we identify two populations of naive CD4 T cells: a long-lived population as well as a short-lived population. In addition, we identify two factors that contribute to the establishment of long-lived naive CD4 T cells. We confirm earlier findings that MHC class II interaction with the TCR on CD4 T cells is important for survival. Furthermore, we find that MHC class II alleles with the correct restriction element for Ag presentation mediate the peripheral survival of naive CD4 T cells more efficiently than other positively selecting alleles, regardless of the selecting MHC in the thymus. The second component contributing to the survival of naive CD4 T cells is contact with the cytokines IL-4 and IL-7. We find that the physiological levels of IL-4 and IL-7 serve to enhance the MHC class II-mediated survival of naive CD4 T cells in vivo.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.162.7.3795